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At least 343 records · Page 19Linked to original sources
PubMed1986

Intimal cell mass-derived atherosclerotic lesions in the abdominal aorta of hyperlipidemic swine. Part 2. Investigation of endothelial cell changes and leukocyte adherence associated with early smooth muscle cell proliferative activity.

We have investigated several aspects of endothelial cell (EC) behavior during the initiation and early development of intimal cell mass (ICM)-derived atherosclerotic lesions in the distal abdominal aortas of young swine fed hyperlipidemic (HL) diets for 0, 14, 49, or 90 days. By scanning electron microscopy no breaks in endothelial integrity or other abnormalities were observed even at 90 days on diet after lesions were well established. Also, counts of leukocytes adherent to the endothelium by both scanning and light microscopy revealed no greater numbers in HL than in mash control swine. Estimates of individual EC losses over ICM-lesions in the HL swine (based on calculations from tritiated thymidine labeling indices and EC growth rates determined by counts) suggested a loss of approximately one per 100 EC/day. This loss over ICM lesion was not significantly greater than that over ICM in mash controls, but was significantly greater than that of EC not over ICM lesions in the same HL animal. In any event, the estimated loss seems to be too trivial for the endothelial barrier to be compromised even transiently in a biologically significant fashion. A significant correlation was observed between tritiated thymidine labeling indices of cells within the ICM lesions and of those of the overlying EC that was not observed with the ICM in the controls. Possibly the positive correlation may be a result of the abluminal surface of the overlying EC being exposed to the abnormal milieu of the ICM lesion. It is emphasized that results reported here apply only to ICM-derived lesions at an early stage of development and that they do not contradict results obtained by others with other lesion types such as those derived from monocytes. Furthermore, in later stages of development of ICM-derived lesions in the same model we know that extensive endothelial cell damage can be demonstrated. Also, functional changes in endothelial permeability may have been present in early stages that would not have been detected with the methods used in this study.

Animals↗
PubMed1988

Endothelial cell denudation, labelling indices and monocyte attachment in advanced swine coronary artery lesions.

This study shows that frank endothelial denudation, as measured by scanning electron microscopy, is associated with coronary artery atherosclerotic lesions in swine fed hyperlipidemic diets for 9 or 18 months. The largest areas of endothelial cell denudation were found to be associated with the most advanced atherosclerotic lesions, and lesser areas of denudation were present in less severely atherosclerotic arteries. Overall, the study suggests that frank endothelial denudation in swine coronaries occurs secondarily to advanced lesion development, and is proportionate to the amount of lesion present. In contrast attachment of monocytes to the endothelial surface was not proportionate to the amount of lesion present. While the number of attached monocytes after 9 or 18 months of a hyperlipidemic diet was much greater than in the mash-fed swine, there was no difference between the two hyperlipidemic groups. In both hyperlipidemic groups, the attached monocytes were concentrated over lesion areas. By scanning electron microscopy, most attached monocytes in these perfused coronary arteries showed a slender foot process extending into a gap between endothelial cells. Endothelial cell turnover, as measured by tritiated thymidine labelling indices, increased with the amount of coronary artery atherosclerosis. However, it did not become significantly greater than in mash-fed swine until advanced lesions developed.

Animals↗
PubMed1977

A rapid quantitative assay for lymphotoxin.

A rapid quantitative assay for lymphotoxin was developed with the use of a mouse cultured lymphoid cell line, L1210 as the target cell. The assay produces results which are substantially in agreement with assays employing fibroblasts as targets. After incubation with lymphotoxin containing samples, target cells were labelled with [3H]thymidine and harvested with a Multiple Automated Sample Harvester (MASH). The MASH allows multiple replicates to be obtained from which the calculation of an I50 (50% inhibition) point and lymphotoxin specific activities can be performed with high statistical reliability by means of probit transformation and analysis.

Animals↗
PubMed1977

Aphagia, behavior sequencing and body weight set point following orbital frontal lesions in rats.

Discrete lesions were made in the orbital frontal neocortex of rats and eating, drinking, sensorimotor responsiveness, and sequencing of motor acts were studied. Duration of aphagia was related to palatability/texture of food. Rats were aphagic for a mean of two days to palatable cookie mash presented on a spatula, six days to a high fat diet mash presented in a 4 cm high dish and for seven days to dry laboratory food. Water drinking was resumed with injestion of dry food. Rats presurgically fattened to 120% of body weight appeared stuporous and akinetic for 2-3 postoperative days, and the period for acceptance of food in tall tests was protracted. Rats presurgically dieted to 80% of normal body weight did not show accelerated recovery of feeding. Preoperatively normal, fattened and dieted rats assumed a chronic postoperative body weight level 25% lower than control rats. Rats with lesions showed sensorimotor neglect when tested on an open table top, but did not show neglect when tested in their home cages. In grooming tests, rats with lesions showed all of the components of normal grooming, but failed to exhibit the long chains of grooming characteristics of control rats. They also showed attenuated tongue extension and had difficulty manipulating food with the forepaws. The experiments suggest that following orbital frontal lesions, motor impairments, motor sequencing dysfunctions, change in body weight set point, and depending upon the test situation, sensorimotor neglect, may all be contributing factors to aphagia. The orbital frontal cortex may influence feeding and other behaviors via descending neural projections to the hypothalamus and branistem.

Animals↗
PubMed1985

Periodic water availability is not a potent zeitgeber for entrainment of circadian locomotor rhythms in rats.

Entrainment of tilt-cage measured circadian activity rhythms to a 2 hr daily period of water availability was assessed in rats fed either an oil-chow mash, which rats readily consume in the absence of water, or dry pellet chow, which rats less readily consume in the absence of water. Four of 6 pellet fed rats but only 2 of 14 mash fed rats exhibited entrainment to water access. Periodic water availability, unlike periodic food availability, thus does not appear to be a potent zeitgeber for circadian activity rhythms in the rat. The entrainment that does occur in some rats may result from shifting of food intake to coincide with the availability of water.

Animals↗
PubMed1993

A microstructural analysis of the effects of presatiation on feeding behavior in the rat.

Rats were familiarized with eating a sweetened mash, and were divided into three groups. Before a test meal, the animals were allowed to eat the mash for 0, 2.5, or 5 min, respectively, to vary the degree of their satiation. Their subsequent consumption of the meal and their behavior over the course of a 30-min period was observed, to provide a microstructural description of the behavioral changes that are characteristic of increasing satiation. Presatiation, as expected, reduced the size of the test meal, and did so predominantly by reducing the duration of feeding, especially during the first 5 min of the test period. There was a slight reduction in the rate of eating as a function of presatiation, and a tendency for the latency to initiate feeding to increase. When other responses were considered separately, there was little effect of presatiation on their microstructural parameters. However, the duration of a composite category (comprising rearing, grooming, and stationary) did increase significantly as a function of presatiation. These data provide a behavioral template for satiation, against which to compare treatments that purport to manipulate feeding satiation.

Animals↗
PubMedDate not supplied

Cafeteria behavior in the rat after hypothalamic cholinergic and adrenergic stimulation.

Norepinephrine, carbachol, or placebo was micro-injected into the perifornical region of the rat hypothalamus, via stereotaxically implanted cannulas. Ingestive behavior was observed in the hour after injection in a cafeteria situation in which water, milk, mash, powdered food, and lab chow were all freely available. After adrenergic stimulation, animals ingested significant amounts of mash only; after cholinergic stimulation, animals ingested significant amounts of water and milk, but water was significantly preferred to milk. These findings are seen as providing further support for the behavioral specificity of direct chemical stimulation of the brain, and as casting serious doubts on the interpretation of milk-ingestion as eating behavior.

Animals↗
PubMed1989

A comparison of the effects of tryptamine and 5-hydroxytryptamine on feeding following injection into the paraventricular nucleus of the hypothalamus.

The effects of 5-hydroxytryptamine (5-HT) and tryptamine injected into the paraventricular nucleus of the hypothalamus (PVN) on food intake, and on noradrenaline- (NA) induced feeding were examined. In nondeprived rats, 12.5-100 nmol 5-HT reduced the intake of palatable wet mash diet over a 30-minute period. Tryptamine (50 and 100 nmol) was without effect in this paradigm. However, when tryptamine was injected into the PVN of rats pretreated with the monoamine oxidase inhibitor, pargyline, a strong anorectic effect was observed. The action of tryptamine in pargyline-treated rats was not affected by depletion of 5-HT levels in the PVN with PCPA. This indicates that the effect of tryptamine is not mediated by a release of endogenous 5-HT. Tryptamine injected into the PVN potentiated the effect of a low dose of 5-HT on food intake. This effect may be due to a prolongation of the activity of 5-HT resulting from tryptamine competing with 5-HT for the same reuptake system. Tryptamine and 5-HT attenuated the feeding response elicited by injection of 25 nmol NA into the PVN. Both tryptamine and 5-HT were more potent at attenuating the effects of NA than in reducing the intake of the palatable wet mash diet. Overall, the results suggest that tryptamine may act via the serotonergic system in the PVN to affect food intake, but it is a weaker compound than 5-HT in this respect.

Animals↗
PubMed1991

Peripheral 5-carboxamidotryptamine (5-CT) elicits drinking by stimulating 5-HT1-like serotonergic receptors in rats.

Subcutaneous administration of the prototypical 5-HT1-like agonist, 5-carboxamidotryptamine (5-CT), increased 2-h water intake by nondeprived rats (ED50 = 0.04 mumol/kg). The 5-HT1 agonists 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT, 0.04-0.32 mumol/kg) and RU 24969 (0.16 mumol/kg) did not produce drinking. The dipsogenic effect of 5-CT (0.08 mumol/kg) was prevented by the 5-HT1/2 antagonist, methysergide (ID50 = 4 mumol/kg), but not by 16 mumol/kg of the 5-HT2 antagonist, ketanserin; the 5-HT21C antagonist, mianserin; or the 5-HT3 antagonist, MDL 72222, 5-CT also increased drinking and reduced food intake when food-deprived rats were given 2-h access to mash. Methysergide (16 mumol/kg) inhibited both actions of 5-CT but an equimolar dose of the 5-HT1/beta adrenergic antagonist, (-)-propranolol, blocked only the drinking. The 5-HT21C antagonist, ritanserin (16 mumol/kg), altered neither ingestive action of 5-CT although, by itself, ritanserin increased mash intake. The results suggest that activating a subtype of peripheral 5-HT1-like receptor stimulates drinking in rats. This receptor is unlike either the 5-HT1A or the 5-HT1C sites found in the brain. Furthermore, the dipsogenic and anorectic actions of 5-CT occur independently.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

The selective 5-HT3 receptor antagonist, ondansetron, augments the anorectic effect of d-amphetamine in nondeprived rats.

Previous behavioural studies have shown that 5-hydroxytryptamine3 (5-HT3) receptor antagonists either block or have no effect on amphetamine-induced effects. The present experiments investigated whether or not the highly selective 5-HT3 receptor antagonist ondansetron would affect the anorectic effect of a small dose (1 mg/kg) of d-amphetamine. Nondeprived male rats were tested in two feeding paradigms: consumption of a palatable sweetened mash and ingestion of a 3% sucrose solution. Ondansetron (10-100 micrograms/kg) did not antagonize amphetamine-induced anorexia; instead, in both paradigms consumption was reduced still further when the 5-HT3 antagonist was given in conjunction with amphetamine. Ondansetron given alone had significant effects on consumption, but the direction of the effect differed according to the paradigm. Sweetened mash intake was significantly increased at 30 and 100 micrograms/kg, while sucrose ingestion was significantly reduced at 10 and 30 micrograms/kg ondansetron. It is suggested that ondansetron has two opposing effects on intake, one of which (hyperphagia) can be masked by d-amphetamine, leaving an anorectic effect that augments that of d-amphetamine.

Animal Feed↗
PubMed1993

Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons.

The mouse Mash-1 gene, like its Drosophila homologs of the achaete-scute complex (AS-C), encodes a transcription factor expressed in neural precursors. We created a null allele of this gene by homologous recombination in embryonic stem cells. Mice homozygous for the mutation die at birth with apparent breathing and feeding defects. The brain and spinal cord of the mutants appear normal, but their olfactory epithelium and sympathetic, parasympathetic, and enteric ganglia are severely affected. In the olfactory epithelium, neuronal progenitors die at an early stage, whereas the nonneuronal supporting cells are present. In sympathetic ganglia, the mutation arrests the development of neuronal precursors, preventing the generation of sympathetic neurons, but does not affect glial precursor cells. These observations suggest that Mash-1, like its Drosophila homologs of the AS-C, controls a basic operation in development of neuronal progenitors in distinct neural lineages.

Adrenal Medulla↗
PubMed1987

Effects of chronic paraventricular nucleus infusion of clonidine and alpha-methyl-para-tyrosine on macronutrient intake.

Earlier studies have demonstrated that acute injections of norepinephrine (NE) and clonidine (CLON) into the paraventricular nucleus (PVN) elicit feeding in satiated rats. This study examined the effects of chronic PVN infusion of alpha-methyl-paratyrosine (alpha-MpT), a catecholamine synthesis inhibitor, on intake of a mixed milk-mash diet and on the ingestion of pure macronutrients, protein, carbohydrate and fat. The impact of chronic CLON administration on intake of these macronutrient preparations was also investigated. Over a 14-day period, chronic infusion of alpha-MpT (50 nmoles/30 sec/0.5 microliter) resulted in a reduction of total daily food intake in rats maintained on a milk-mash diet. Chronic administration of CLON (3 nmoles/30 sec/0.5 microliters) was observed to produce a specific increase in ingestion of the carbohydrate, along with a suppression in the intakes of the protein and fat. These results are similar to those previously demonstrated for NE. In contrast, chronic infusion of alpha-MpT into the PVN caused a specific reduction of carbohydrate consumption and an enhancement of protein ingestion, with fat intake unaffected. This evidence suggests that the alpha 2-noradrenergic system of the PVN plays an important role in the daily regulation of macronutrient intake, specifically of carbohydrate.

Animals↗
PubMed1980

Cholecystokinin acts on the hypothalamic "noradrenergic system" involved in feeding.

In male long Evans rats, microinjection cannulae were stereotaxically positioned to rest in sites in the preoptic area and medial hypothalamus. After the rats were satiated on wet mash, norepinephrine (NE) was infused in a dose of 2.5 micrograms and a volume of 0.75 microliter into these diencephalic sites. At loci in six animals, NE evoked spontaneous feeding of 5.0 gms or more of wet mash. Cholecystokinin (CCK) infused prior to the NE microinjection either intraperitoneally (0.5--1.0 microgram/kg) or at the NE-sensitive hypothalamic sites (75--150 ng) significantly attenuated or blocked the rat's feeding response to NE. The intake of water was unaffected by CCK in both instances. Thus, CCK may act on the diencephalic noradrenergic feeding system indirectly, through vagal afferent pathways, or directly within the animal's hypothalamus.

Animals↗
PubMed1992

Social stress and atherosclerosis in roosters.

1. Socially stressed roosters fed either plain mash or an atherogenic diet had a greater incidence and severity of aortic atherogenesis than similarly fed non-stressed birds. 2. Results demonstrated a significant atherogenic effect of stress in chickens even in the absence of hyperlipidaemia. 3. Lack of appreciable differences in plasma lipids between stressed and non-stressed birds suggested that the atherogenic effects of stress may be attributable to neuroendocrine responses. 4. Levels of HDLc of plain mash groups were significantly higher than in the atherogenic fed groups. 5. Haemodynamic data showed no treatment-related differences.

Animals↗
PubMed1986

Effects of phenylpropanolamine on gastric retention in the adult rat.

Phenylpropanolamine (PPA) induces anorexia and weight loss via an as yet unidentified mechanism. In the present study, we evaluated the inhibitory action of PPA on gastric emptying. Adult female Sprague-Dawley rats consumed a wet-mash test meal and were then treated (IP) with either saline or 5, 10, 20 or 40 mg/kg PPA. Gastric retention (ratio of weight of gastric content to weight of mash consumed) was evaluated immediately after the meal in a group of saline-treated rats or 3 hours after the meal in the drug groups and another saline-treated group. Rats treated with saline exhibited minimal retention (0.21) over a 3 hour period whereas rats treated with 5, 10, 20 or 40 mg/kg dl-PPA exhibited increased gastric retention ratios of 0.29, 0.66, 0.63, and 1.38, respectively. These data demonstrate that PPA has a marked inhibitory action on gastric emptying and suggest that further studies are warranted to evaluate the possible contribution of gastric retention to the anorexic action of PPA.

Animals↗
PubMed2005

Anorexia and weight loss in male rats 24 h following single dose treatment with orexin-1 receptor antagonist SB-334867.

Acute systemic treatment with the selective orexin-1 receptor antagonist SB-334867 (30 mg/kg, i.p.) has been reported not only to inhibit food intake and to accelerate behavioural satiety in rats, but also to produce a significant loss of bodyweight over the 24 h period post-dosing. The present studies were designed to test the hypothesis that the inhibition of weight gain following acute treatment with SB-334867 is due to a persistent anorectic action of the compound. In Experiment 1, the acute effects of SB-334867 (30 mg/kg, i.p.) on food intake and behaviour in a 1 h test with palatable mash were assessed as a function of injection-test interval. Results confirmed that, when administered 30 min prior to testing, SB-334867 significantly suppressed mash intake and accelerated behavioural satiety. More importantly, significant anorexia and behavioural change were also observed when animals were tested 24 h, but not 48 h, post-dosing. As previously reported, all animals treated with the orexin-1 receptor antagonist lost bodyweight over the 24 h period following acute treatment. The generality of these findings was confirmed in Experiment 2, where acute treatment with SB-334867 (30 mg/kg, i.p.) significantly suppressed home cage chow consumption over the 24 h period post-dosing, an effect also accompanied by a significant loss of bodyweight. The results of Experiment 3 showed that, following i.p. administration of 30 mg/kg, SB-334867 has good CNS penetration, reaches peak plasma and brain concentrations at 30 min, and maintains good exposure over 4 h post-dosing. Overall, current data support the hypothesis that a persistent anorectic action contributes to the significant loss of bodyweight observed 24 h following acute dosing with SB-334867. As the compound is virtually undetectable in plasma or brain beyond 8 h post-dosing, and since nothing is known about potentially active metabolites, we consider the possibility that single dose treatment with SB-334867 results in enduring alterations to the orexin-1 receptor and/or downstream signalling pathways.

Activity Cycles↗
PubMed2005

Food type, food preparation, and competitive food purchases impact school lunch plate waste by sixth-grade students.

Because plate waste reduces nutritional benefits of school lunches, the objective of this study was to determine the factors that influence waste. Lunches of 743 sixth graders in three middle schools were photographed after students made food selections and after eating. Sample items were purchased to determine initial portion weights. The Statistical Package for Social Sciences software (Base 10.0, 1995, SPSS Inc, Chicago, IL) was used for statistical analysis. Preparation method influenced acceptance rates and plate waste: Whole apples had lower acceptance (23%) and greater waste (62%) compared with applesauce (37% acceptance, 23% waste). Mashed potatoes and heated fries had similar acceptance (approximately 69%), but mashed potatoes were wasted less (19% vs 33%, respectively). Students who purchased competitive food items with lunch (n = 250) had significantly greater waste of fruits (52% vs 36%, respectively, P = .0001), grain products (26% vs 14%, respectively, P = .009), meats (25% vs 16%, respectively, P = .015), and mixed dishes (30% vs 18%, respectively, P = .0001). Changing preparation methods and limiting availability of competitive food items may reduce plate waste.

Animals↗
PubMed2004

Differential effects of the selective orexin-1 receptor antagonist SB-334867 and lithium chloride on the behavioural satiety sequence in rats.

Recent studies have shown that acute systemic administration of the selective orexin-1 receptor antagonist SB-334867 significantly reduces food intake in rats. Although this anorectic action of orexin-1 receptor blockade is associated with an acceleration in the transition from eating to resting, it is widely recognised that the behavioural indices of satiety are not dissimilar to those of illness. In this context, Experiment 1 confirmed a significant anorectic effect of 90 (but not 60) mg/kg lithium chloride (LiCl) in male rats presented with palatable mash in the home-cage environment. Experiment 2 employed a continuous monitoring technique to contrast the effects of LiCl (90 mg/kg) and SB-334867 (10 and 30 mg/kg) on food intake and behaviour during a 1-h test with palatable mash. SB-334867 dose-dependently inhibited food intake, with the higher dose producing a comparable degree of appetite suppression (approximately 40%) to that seen with LiCl. Despite equivalent anorectic action, the two compounds produced very different effects on behaviour. LiCl reduced active behaviours (locomotion, rearing, grooming and sniffing), slowed the rate of eating and disrupted the behavioural satiety sequence (BSS). In contrast, SB-334867 (30 mg/kg) decreased the duration of feeding and grooming, and modestly accelerated the transition between eating and resting. Furthermore, whereas LiCl failed to alter posttreatment bodyweight gain, SB-334867 (30 mg/kg) produced a significant weight loss in the 24-h period immediately following injection. Overall, the divergent profiles obtained with equianorectic doses of LiCl and SB-334867 provide convincing evidence for the behavioural selectivity of SB-334867-induced anorexia.

Animals↗